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The IBM Research Division has developed the Resource Capacity Planning (RCP) Optimizer to support the Workforce Management Initiative (WMI) of IBM. RCP applies supply chain management techniques to the problem of planning the needs of IBM for skilled labor in order to satisfy service engagements, such as consulting, application development, or customer support. This paper describes two RCP models and presents two approaches to solving each of them. We also describe the motivation for using one approach over another. The models are built using the Watson Implosion Technology toolkit, which consists of a supply chain model, solvers for analysis and optimization, and an Application Programming Interface (API) for developing a solution. The models that we built solve two core resource planning problems, gap/glut analysis and resource action planning. The gap/glut analysis is similar to material requirements planning (MRP), in which shortages (gaps) and excesses (gluts) of resources are determined on the basis of expected demand. The goal of the resource action planning problem is to determine what resource actions to take in order to fill the gaps and reduce the gluts. The gap/glut analysis engine is currently deployed within the IBM service organization to report gaps and gluts in personnel.

Autocrine growth stimulation by IGF-II and BDNF is frequently observed in neuroblastoma. The signals of the receptors of these growth factors are transduced to the nucleus via the Ras-MAP-kinase pathway where they induce proliferation. Inactivation of Ras-proteins by farnesyltransferase inhibitors such as FTI-277 disrupts growth stimulation of ras-transformed cells. We investigated whether FTI-277 is also active against tumor cells with constitutively activated growth factor receptors but lacking ras-mutations.We analyzed eight different neuroblastoma cell lines for the expression of BDNF and its receptor trkB. Two of these cell lines with a complete autocrine BDNF loop were treated with FTI-277, and the effects of Ras-inactivation on the signal transduction of BDNF were analyzed.Treatment of neuroblastoma cells with 10 microM FTI-277 for 4 days reduced the amount of membrane-bound Ras-protein to almost 50%. Activation of MAP-kinase, induction of N-myc expression, and proliferation were clearly reduced in the treated cells. In addition, we observed some cytotoxic effects of FTI-277 accompanied by morphological changes of the neuroblastoma cells and a delayed induction of apoptosis.Farnesyltransferase inhibitors are active against neuroblastoma cells but the mechanism of action is not limited to inactivation of Ras. Further investigations on the targets of FTI-277 are recommended.

In vitro susceptibility assays of herpes simplex virus (HSV) do not necessarily correlate with treatment outcome. An HSV type 1 (HSV-1) isolate, N4, recovered from a patient who presented with herpes keratitis with localized immunosuppression, was characterized for susceptibility. Although the 50% inhibitory concentration (IC(50)) for this isolate was less than the accepted breakpoint for defining resistance to acyclovir (>2.0 microg/mL), the following lines of evidence suggest that the isolate was acyclovir resistant: (1) the clinical history confirmed that the infection was nonresponsive to acyclovir; (2) the in vitro susceptibility was similar to that of a thymidine kinase (TK)-negative, acyclovir-resistant virus SLU360; (3) the IC(50) of acyclovir was more than 10 times the IC(50) for an acyclovir-susceptible control strain; (4) plaque-purified clonal isolates were resistant to acyclovir (IC(50)s, >2.0 microg/mL); and (5) biochemical studies indicated that the HSV-1 N4 TK was partially impaired for acyclovir phosphorylation. Although residue changes were found in both the viral tk and pol coding regions of HSV-1 N4, characterization of a recombinant virus expressing the HSV-1 N4 polymerase suggested that the TK and Pol together conferred the acyclovir-resistance phenotype.

This paper describes Orchard, which is a heuristic algorithm for scheduling the loading of jobs into a manufacturing system. While Orchard was specifically designed for use at a particular printed circuit board line, it is sufficiently generic to be used at other manufacturing systems as well. In general, such a manufacturing system performs several operations on each job with multiple machines performing each operation. The routing of each job may involve stochastic branching including rework loops, and there may be a need to assign human operators to operations. The Orchard heuristic can be adapted to two different objective functions: weighted mean flow time, and an objective specially formulated for the circuit board line. The present paper describes all aspects of Orchard except its operator assignment module (which is described in another paper) and concludes with results of tests of the algorithm as applied to the circuit board line.

This note addresses a problem of assigning human operators to operations in a manufacturing system. The problem involves a set of operations, a work load for each operation, and a set of human operators, each skilled at a subset of the operations. The task is to assign the operators to the operations so as to maximize the capacity of the system, robustly. The problem is formulated as a network flow problem with a lexicographic objective. It is then shown how to solve this problem very efficiently as a parametric sequence of network maximum flow problems, by application of the “parametric preflow” algorithm of Gallo, Grigoriadis and Tarjan.

Background The thymidine kinase (tk) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1. Methods A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol) within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases. Results Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAAr5 exhibited a 2–4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed signficant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA stucture. Conclusions This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a) mutations may be modulated by other viral polypeptides cooperating with Pol, and (b) the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2.

Consider a manufacturing line that produces parts of several types. Each part must be processed by at most one machine in each of several banks of machines. This paper presents an algorithm that schedules the loading of parts into such a line. The objective is primarily to minimize the makespan and secondarily to minimize queueing. The problem is decomposed into three subproblems and each of these is solved using a fast heuristic. The most challenging subproblem is that of finding a good loading sequence, and this is addressed using workload concepts and an approximation to dynamic programming. We make several extensions to the algorithm in order to handle limited storage capacity, expediting, and reactions to system dynamics. The algorithm was tested by computing schedules for a real production line, and the results are discussed.